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Anna Matynia, Sachin Parikh, Samer Habib, Paul Kim, Steven Nusinowitz, Michael Gorin; Ocular surface damage and migraine preclinical mouse models of photophobia. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5763.
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Light sensitivity negatively impacts productivity and quality of life, and is a clinical problem of increasing concern and interest. As many as 50% of mild traumatic brain injury patients, 80% of migraine patients and many patients with ocular inflammation or trauma experience photoallodynia, a painful response to normal light. We aim to establish mouse models of ocular (corneal surface injury) and central (migraine) etiologies using light aversion as an endophenotype of photoallodynia, and ultimately use them to investigate molecular and neural mechanisms.
A customized light aversion behavioral test was used to assess photosensitivity in wild type and ipRGC-ablated mice with corneal application of benzalkonium chloride (BAC, ocular damage) or injection of nitroglycerin (NTG, migraine). Full-field electroretinography (ERG) was performed on NTG-injected animals. Corneal sensitivity was tested using von Frey Fibers.
Corneal damage from BAC causes increased ipRGC-dependent light aversion (2% BAC, 1 day acute treatment, n=7). Lower levels of BAC (0.25%, n=5 and 0.50%, n=4) show a trend towards increased ipRGC-dependent light aversion after 1 day but not 7 days of treatment. There is a trend for decreased corneal sensitivity with 2% BAC (n=6 eyes) after 1 day but not with 0.25% (n=8 eyes) or 0.5% (n=10 eyes) after 7 days. Additional animals will be tested for light aversion and corneal sensitivity after BAC treatment. Mice with NTG-induced migraine (n=9) exhibit increased ipRGC-independent light aversion that is resistant to treatment with sumatriptan (n=8), a migraine medication. No differences in ERGs were observed using the same dose of NTG. Chronic treatment with NTG (n=6) compared to vehicle (n=6) does not sensitize light aversion.
These studies establish two clinically relevant mouse models of photoallodynia. In BAC-treated mice, light aversion may be an early symptom of damage. In migraine, the mechanisms that underlie light aversion may be different from other migraine symptoms such as headache. The results indicate that ipRGCs mediate some but not all forms of light aversion, indicating that more than one retinal-brain circuit can elicit light aversion. Their role in specific etiologies of photoallodynia may help elucidate these differential retinal-brain circuits and provide insights to potential clinical classification and management of photoallodynia.
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